Vaccine microarray patch self-administration: An innovative approach to improve pandemic and routine vaccination rates.

The high-density microprojection array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. HD-MAPs provide an alternative to needle and syringe (N&S) vaccination. Additional advantages could include reduced cold-chain requirements, reduced vaccine dose, reduced vaccine wastage, an alternative for needle phobic patients and elimination of needlestick injuries. The drivers and potential benefits of vaccination by self-administering HD-MAPs are high patient acceptance and preference, higher vaccination rates, speed of roll-out, cost-savings, and reduced sharps and environmental waste. The HD-MAP presents a unique approach in pandemic preparedness and routine vaccination of adults. It could alleviate strain on the healthcare workforce and allows vaccine administration by minimally-trained workers, guardian or subjects themselves. Self-vaccination using HD-MAPs could occur in vaccination hubs with supervision, at home after purchasing at the pharmacy, or direct distribution to in-home settings. As a result, it has the potential to increase vaccine coverage and expand the reach of vaccines, while also reducing labor costs associated with vaccination. Key challenges remain around shifting the paradigm from medical professionals administrating vaccines using N&S to a future of self-administration using HD-MAPs. Greater awareness of HD-MAP technology and improving our understanding of the implementation processes required for adopting this technology, are critical factors underpinning HD-MAP uptake by the public.

Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

The effect of exercise on local and systemic adverse reactions after vaccinations - Outcomes of two randomized controlled trials.

INTRODUCTION: An adverse reaction associated with vaccination is considered to be a key barrier to vaccinate, yet little attention has been given to interventions to reduce their occurrence. Exercise is a behavioural adjuvant which may also influence adverse reactions. Here, two randomized controlled trials are reported, examining the effects of exercise on self-reported adverse reactions following vaccination in adolescents and young adults. METHODS: Study one; 116 adolescents receiving the HPV vaccine were randomly allocated to either Control (n = 56) or Pre-vaccine Exercise (n = 60) group (2015-2016). Exercise consisted of 15-minutes upper body exercise. Study two; 78 young adults receiving the influenza vaccine were randomly allocated to either Control (n = 19), or one of 3 exercise groups: Pre-vaccine Arm (n = 19), Pre-vaccine Leg (n = 20) or Post-vaccine Arm (n = 20) (2017). Exercise included 15-minutes of arm or leg exercises prior to or after vaccination. All participants in both studies completed an adverse events diary for seven-days post-vaccination. RESULTS: Study one; Reported days of tenderness in female adolescents that exercised were significantly lower than control (p = 0.032), with a similar trend in reported days of pain (p = 0.050). Furthermore, days of feeling ill (p = 0.070) and reduced appetite (p = 0.067) were found to be lower with exercise, although not significant. Overall, female adolescents reported significantly more days of pain (p = 0.003), tenderness (p < 0.001), swelling (p = 0.011), and feeling ill (p = 0.0040). Study two; Exercise groups reported reduced days of swelling (p = 0.018), fever (p = 0.013), and lowered appetite (p = 0.011) across both genders. Furthermore, females reported reduced days of medication use with exercise (p = 0.034), and a trend toward reduced days of swelling (p = 0.052). DISCUSSION: In two separate trials, a short bout of exercise reduced reported adverse reactions after vaccinations for local and systemic adverse reactions. Gender differences in reported local and systemic adverse reactions were more evident among adolescents than young adults. These findings support the need for further work to examine the potential benefit of exercise in improving vaccination procedures.

Development and validation of measures to evaluate adolescents' knowledge about human papillomavirus (HPV), involvement in HPV vaccine decision-making, self-efficacy to receive the vaccine and fear and anxiety.

OBJECTIVES: We describe the development and validation of measures of human papillomavirus (HPV)/HPV vaccination knowledge, fear/anxiety about vaccination, involvement in HPV vaccine decision-making, and self-efficacy with regard to getting the vaccine, designed to evaluate the efficacy of an intervention to affect these domains (collectively termed the HAVIQ: HPV Adolescent Vaccine Intervention Questionnaire). STUDY DESIGN: Literature search, cognitive interviews and cross-sectional survey. METHODS: A literature search identified existing items that were modified for the present measures. Experts reviewed draft measures for face and content validity. Cognitive interviews with adolescents were also used to assess content validity. Adolescents completed the measures and an internal reliability analysis of each measure was performed. RESULTS: The four experts concurred that the measures had face validity. Cognitive interviews identified items requiring refinement. Content validity was examined with ten experts and was deemed acceptable. There were 1800 adolescents who completed the measures; Cronbach's alpha was >0.6 for three of the four measures. The four final measures are brief, comprising 25 items in total. CONCLUSIONS: The measures are robustly developed and validity-tested. The HAVIQ may be used in research settings to evaluate adolescents' knowledge and experiences of the process of HPV vaccination in a school-based vaccination programme.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.

Randomised controlled trial of an educational strategy to increase school-based adolescent hepatitis B vaccination.

OBJECTIVES: This study aimed to evaluate a specifically designed hepatitis B education/promotion curriculum package as part of a successful hepatitis B vaccination delivery system to adolescents. METHODS: A randomised-controlled trial was used to evaluate the effect of the curriculum package (or intervention) on uptake of vaccine. Schools were randomly selected from the metropolitan region of Melbourne to intervention (66 schools or 7,588 students) or control groups (69 schools or 9,823 students). Class teachers administered the intervention to students over 4 class periods before the vaccination course. RESULTS: The difference in mean school uptake between intervention and control was small at 1-2% per dose. 95% confidence intervals around the differences were -5% to 2% per dose and not significant. Intervention schools taught an average of 7 items out of 12 from the curriculum package. Immunisation rates increased by 4-10% per dose between low and high implementation schools, but this trend was not significant. Impact evaluation demonstrated significantly greater knowledge of hepatitis B and vaccination among students in the intervention than the control group. CONCLUSION: Hepatitis B vaccination of pre-adolescents was not increased by the implementation of a curriculum package that successfully increased knowledge and awareness of hepatitis B in a school-based vaccination program. Additional strategies directed at the education of parents, the cooperative role of schools and pro-active providers might also be required to maximise vaccine uptake in this age group.

Reinforcement and backpropagation training for an optical neural network using self-lensing effects.

The optical bench training of an optical feedforward neural network, developed by the authors, is presented. The network uses an optical nonlinear material for neuron processing and a trainable applied optical pattern as the network weights. The nonlinear material, with the applied weight pattern, modulates the phase front of a forward propagating information beam by dynamically altering the index of refraction profile of the material. To verify that the network can be trained in real time, six logic gates were trained using a reinforcement training paradigm. More importantly, to demonstrate optical backpropagation, three gates were trained via optical error backpropagation. The output error is optically backpropagated, detected with a CCD camera, and the weight pattern is updated and stored on a computer. The obtained results lay the ground work for the implementation of multilayer neural networks that are trained using optical error backpropagation and are able to solve more complex problems.

Forearm muscle activation during power grip and release.

The position of the hand during power grip is well-described, but the normal phasic activity of the extrinsic forearm muscles during power grip and release is unknown. People with neurologic impairment may have inadequate power grip or release because of abnormal muscle timing. This study describes the timing of the forearm muscles in 10 normal subjects during power grip and release, which was evaluated using electromyography. During power grip, subjects had consistent timing patterns for extrinsic finger motors and different but individually consistent patterns for wrist motors. This finding supports our hypothesis that different individuals habitually use a specific motor strategy and an intact central nervous system allows them to change their motor strategy to adapt to new environmental parameters.

Results of hip arthrodesis in adolescents by using the cobra-head plate for internal fixation.

A retrospective study was conducted to examine the efficacy and potential morbidity of hip fusion using the Cobra-head plate in adolescents. A heterogeneous group of 11 adolescents, with recalcitrant hip pain and an average age of 14.6 years, underwent unilateral hip arthrodesis with the Cobra-head plate for internal fixation. Seven (64%) patients achieved an uneventful clinical and radiographic arthrodesis after a mean postoperative interval of 7.4 months. Four index operations (36%) were complicated by pseudarthrosis. All patients who developed a postoperative pseudarthrosis ranked at or above the 90th percentile for their age-determined weight. The relationship between the percentile-weight-for-age and the incidence of pseudarthrosis was statistically significant (p < or = 0.001). Hip-arthrodesis procedures with the Cobra-head plate in adolescents at or above the 90th percentile weight-for-age are associated with an unacceptably high rate of pseudarthrosis. In this subset of patients, alternate or supplementary stabilization methods should be considered.

Measles-mumps-rubella and hepatitis B vaccination uptake in adolescents: a survey in metropolitan Melbourne.

OBJECTIVE: To measure the uptake of preadolescent measles-mumps-rubella (MMR) and adolescent hepatitis B vaccinations and assess the influence of certain demographic factors on the uptake of these vaccines. DESIGN: Prevalence surveys of uptake rates of preadolescent (school Year 6; age 10-11 years) MMR and adolescent (school Year 9; age 13-14 years) hepatitis B vaccination. SETTING: City of Darebin, an inner northern metropolitan region of Melbourne, 1996. SUBJECTS: 1160 Year 6 school students (580 boys) and 1102 Year 9 school students (548 boys). INTERVENTION: School-based vaccination program administered by Darebin Council. RESULTS: 83% of Year 6 students were vaccinated with the MMR vaccine (84.1% of girls and 81.9% of boys). 71.6% of Year 9 students completed the full course of hepatitis B vaccination (68.9% of boys and 74.2% of girls). There was a higher uptake of MMR in non-government primary schools, but no other demographic factors (sex, economic status, non-English-speaking background, parental education, school class size) were associated. CONCLUSIONS: These uptake rates do not meet National Health and Medical Research Council (NHMRC) recommendations. Further study is required to determine and quantify the factors that affect vaccination uptake in adolescence. Programs may then be developed to improve vaccination uptake.

A comparison of gait with solid, dynamic, and no ankle-foot orthoses in children with spastic cerebral palsy.

BACKGROUND AND PURPOSE: This study compared the effects of dynamic ankle-foot orthoses (DAFOs) with a plantar-flexion stop, polypropylene solid ankle-foot orthoses (AFOs), and no AFOs on the gait of children with cerebral palsy (CP). These orthoses were used to reduce the excessive ankle plantar flexion during the stance phase of gait. SUBJECTS AND METHODS: Ten children with spastic CP (6 with diplegia and 4 with hemiplegia) were tested after wearing no AFOs for an initial 2-week period, solid AFOs for 1 month, no AFOs for an additional 2 weeks, and DAFOs for 1 month. The effects of the two orthoses and no AFOs on lower-extremity muscle timing, joint motions, and temporal-distance characteristics were compared. RESULTS: Both orthoses increased stride length, decreased cadence, and reduced excessive ankle plantar flexion when compared with no orthoses. No differences were found for the gait variables when comparing the two orthoses. CONCLUSION AND DISCUSSION: Based on the data, the authors believe that although both orthoses would be recommended for children with spastic CP and excessive ankle plantar flexion during stance, additional individual factors should be considered when selecting either orthosis.

Phasic relationships of the intrinsic and extrinsic thumb musculature.

Dynamic electromyography has proven to be useful in testing patients with spastic disorders who are candidates for tendon transfer or lengthening operations. The purpose of this investigation was to define the normal phasic activity of the thumb muscles during simple, reproducible activities. Fine wire electrode pairs were inserted into the extensors pollicis longus and brevis, abductors pollicis longus and brevis, flexors pollicis longus and brevis, opponens pollicis, adductor pollicis, and first dorsal interosseus of 5 normal subjects. Motions of the carpometacarpal joint and the interphalangeal joint of the thumb were recorded by electrogoniometer. Proximal joint positions were controlled by the subject at the elbow, forearm, and wrist. Normal timing was described for each muscle during hand opening and closing, key pinch with and without force, and opposition pinch with and without force. The data support the concept of individual motor strategies: normal persons often select different combinations of muscles to accomplish a functional goal.

EMG investigation of the effects of peripheral feedback on goal-directed wrist movements.

The objective of this investigation was to determine whether timing of the wrist musculature could be altered when changing the goal of the movement or the sensory feedback needed to complete the movement. Electromyographic (EMG) data from seven wrist and finger muscles as well as simultaneous wrist and finger joint positions were recorded from five normal adults. Subjects performed wrist flexion and extension through different arcs of motion, as fast as possible against a physical stop, and as accurately as possible using visual feedback for speed and joint position. Next, the tonic vibratory reflex was elicited and topical anaesthetic spray was applied; no changes were observed afterwards. The subjects then repeated the wrist movements, and it was evident that activation of agonist and antagonist muscle groups varied according to the goal of the movement.

Neural network implementation using self-lensing media.

An all-optical implementation of a feed-forward artificial neural network is presented that uses self-lensing materials in which the index of refraction is irradiance dependent. Many of these types of material have ultrafast response times and permit both weighted connections and nonlinear neuron processing to be implemented with only thin material layers separated by free space. Both neuron processing and weighted interconnections emerge directly from the physical optics of the device. One creates virtual neurons and their connections simply by applying patterns of irradiance to thin layers of the nonlinear media. This is a result of a variation of the refractive-index profile of the self-lensing nonlinear media in response to the applied irradiance. An optical-backpropagation training method for this network is presented. The optical backpropagation is a training method that can be implemented potentially within the same optical device as the forward calculations, although several issues crucial to this po sibility remain to be addressed. Such a network was numerically simulated and trained to solve many benchmark classification problems, and some of these results are presented. To demonstrate the feasibility of building such a network, we also describe experimental work in the construction of an optical network trained to perform a logic XNOR function. This network, as a proof of concept, uses a relatively slow thermal nonlinear material with ~1-s response time.

Latent onset unilateral toe-walking secondary to hemangioma of the gastrocnemius.

Acquired unilateral pes planus due to hemangioma of the gastrocnemius is an unusual and rarely reported event. In recent years, three children with latent onset unilateral toe-walking due to hemangioma of the proximal gastrocnemius have received treatment at our facility. This report details the usual clinical syndrome and presents postsurgical results. Our experience suggests that in children, a presumptive diagnosis of benign hemangioma of gastrocnemius can be predicated on the basis of history, clinical examination, imaging studies, and laboratory assessment. In contrast to previous reports recommending primary tumor resection, isolated open tendoachilles lengthening can provide acceptable results with minimum morbidity.

Gait analysis in pediatric lower extremity amputees.

Walking function in 56 children with lower extremity amputations was assessed using a questionnaire and gait analysis. Children with prosthetic lower extremities can be very functional in society, often participating in sports. Limitations are proportional to the extent of the missing limbs. As a group, pediatric amputees walk more slowly than their normal peers with a slower cadence and a longer stride length. Pediatric amputees have higher heart rates when walking than normal children, but they seem willing to pay a higher physiologic price for ambulation.